Réaction #69063

Équation de réaction

3-Hydroxybenzaldehyde

DMF

potassium carbonate

potassium iodide

(chloromethyl)cyclopropane

→

title compound

(3-(cyclopropylmethoxy)phenyl)(phenyl)methanamine

Solvants

water

Conditions de réaction

Traitement

1. 1
   Extractionthe resultant mixture was then extracted with toluene (30 mL)
2. 2
   LavageThe organic layer was washed with brine (20 mL)
3. 3
   Séchagedried over anhydrous sodium sulfate
4. 4
   Concentrationconcentrated under reduced pressure
5. 5
   workup.DISSOLUTIONThe residue was dissolved in THF (3.0 mL)
6. 6
   workup.ADDITIONTo the mixture, a solution of phenylmagnesium bromide in THF (1.0 M, 22.6 mL) was added dropwise at 0° C.
7. 7
   workup.STIRRINGthe mixture was stirred at room temperature for 2 hours
8. 8
   workup.ADDITIONTo the reaction mixture, an aqueous saturated ammonium chloride solution (10 mL) was added at 0° C.
9. 9
   Extractionthe resultant mixture was then extracted with ethyl acetate (50 mL)
10. 10
    LavageThe organic layer was washed with brine (30 mL)
11. 11
    Séchagedried over anhydrous sodium sulfate
12. 12
    Concentrationconcentrated under reduced pressure
13. 13
    AutreThe residue was purified by silica gel column chromatography (40% ethyl acetate/hexane)
14. 14
    workup.DISSOLUTIONThe obtained compound was dissolved in chloroform (30 mL)
15. 15
    workup.ADDITIONTo the solution, sodium azide (3.5 g) was added
16. 16
    workup.ADDITIONTo the reaction mixture, trifluoroacetic acid (6.6 mL) was added dropwise at 0° C.
17. 17
    workup.STIRRINGthe mixture was then stirred at room temperature for 1 hour
18. 18
    workup.ADDITIONTo the reaction mixture, water (20 mL) was added
19. 19
    Extractionthe resultant mixture was then extracted with chloroform (20 mL)
20. 20
    LavageThe organic layer was washed with an aqueous saturated sodium bicarbonate solution (20 mL)
21. 21
    Séchagedried over anhydrous sodium sulfate
22. 22
    Concentrationconcentrated under reduced pressure
23. 23
    AutreThe residue was purified by silica gel column chromatography (20% ethyl acetate/hexane)
24. 24
    workup.DISSOLUTIONThe obtained compound was dissolved in methanol (30 mL)
25. 25
    workup.ADDITIONTo the solution, 10% palladium-carbon (600 mg) was added
26. 26
    workup.STIRRINGthe reaction mixture was stirred at room temperature for 2 hours under a hydrogen atmosphere
27. 27
    AutreThe precipitate was removed by filtration through a pad of Celite
28. 28
    Lavagewashed with methanol (100 mL)
29. 29
    ConcentrationThen, the combined filtrate was concentrated under reduced pressure

Mode opératoire

3-Hydroxybenzaldehyde (2.5 g) was dissolved in DMF (25 mL). To the solution, potassium carbonate (6.2 g), potassium iodide (350 mg), and (chloromethyl)cyclopropane (2.1 mL) were added, and the mixture was stirred at 90° C. for 4 hours. To the reaction mixture, water (30 mL) was added, and the resultant mixture was then extracted with toluene (30 mL). The organic layer was washed with brine (20 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was dissolved in THF (3.0 mL). To the mixture, a solution of phenylmagnesium bromide in THF (1.0 M, 22.6 mL) was added dropwise at 0° C., and the mixture was stirred at room temperature for 2 hours. To the reaction mixture, an aqueous saturated ammonium chloride solution (10 mL) was added at 0° C., and the resultant mixture was then extracted with ethyl acetate (50 mL). The organic layer was washed with brine (30 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (40% ethyl acetate/hexane). The obtained compound was dissolved in chloroform (30 mL). To the solution, sodium azide (3.5 g) was added. To the reaction mixture, trifluoroacetic acid (6.6 mL) was added dropwise at 0° C., and the mixture was then stirred at room temperature for 1 hour. To the reaction mixture, water (20 mL) was added, and the resultant mixture was then extracted with chloroform (20 mL). The organic layer was washed with an aqueous saturated sodium bicarbonate solution (20 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20% ethyl acetate/hexane). The obtained compound was dissolved in methanol (30 mL). To the solution, 10% palladium-carbon (600 mg) was added, and the reaction mixture was stirred at room temperature for 2 hours under a hydrogen atmosphere. The precipitate was removed by filtration through a pad of Celite and washed with methanol (100 mL). Then, the combined filtrate was concentrated under reduced pressure to obtain the title compound (2.79 g) as a crude product.

Source